The refractory period is an interval following a paced or spontaneous depolarization of the heart during which delivery of electrical stimulation to the heart is generally ineffective to cause a second depolarization. The refractory period is divided into an absolute refractory period during which no amount of electrical stimulation delivered to the heart will induce a corresponding depolarization, and relative refractory during which electrical stimulation delivered to the heart at an adequate energy level triggers a depolarization. As used herein, the term “refractory period” refers to a period of time that includes both the absolute and relative refractory periods.
A medical device, such as an implantable cardiac pacemaker, can be used to deliver extra-systolic stimulation to the heart. Typically, extra-systolic stimulation is delivered in the form of pulses to a chamber of the heart an extra-systolic interval (ESI) after a paced or spontaneous systolic depolarization of that chamber. Extra-systolic Stimulation (ESS) therapy involves delivery of extra-systolic stimulation after the refractory period, and results in a second depolarization without an attendant myocardial contraction, e.g., a non-systolic depolarization. Because it results in an electrical depolarization, the extra-systolic stimulation may be referred to as “excitatory.” Delivery of extra-systolic stimulation within the refractory period does not result in a depolarization, and is therefore often referred to as non-excitatory stimulation (NES).
The second depolarization of the chamber resulting from delivery of a ESS therapy pulse effectively slows the heart rate from its spontaneous rhythm, allowing a greater time for filling of the chamber. Further, the second depolarization of the chamber causes a augmentation of contractile force of the chamber during the heart cycle following the one in which the ESS therapy pulse is applied. Increased filling and contractile force augmentation can lead to increased cardiac output, particularly when ESS therapy is delivered to one or more of the ventricles of the heart. NES is also believed to increase cardiac output, although to a lesser extent than ESS therapy, by increasing the sympathetic output to the heart. For this reason, ESS therapy and NES have been proposed as a therapy for patients with congestive heart failure (CHF) and/or left ventricular dysfunction (LVD).
The magnitude of the enhanced augmentation resulting from delivery of ESS therapy is strongly dependent on the timing of delivery of the extra-systolic pulse relative to the end of the refractory period. In particular, the magnitude of the enhanced augmentation decreases as the extra-systolic pulse is delivered further from the end, e.g., boundary, of the refractory period. The length of the refractory period can vary between patients, and changes for a particular patient over time based on the physiological condition and activities of the patient. For example, the length of the refractory period can change after resuscitation of the patient, while the patient is taking medications, and while the patient is exercising.